RT Journal Article
SR Electronic
T1 Potential treatment approaches for malignant peritoneal mesothelioma: <em>in vivo</em> and <em>in vitro</em> experimental study of natural killer cell immunotherapy
JF Cancer Biology &amp; Medicine
JO Cancer Biology &amp; Medicine
FD China Anti-Cancer Association
SP 20240218
DO 10.20892/j.issn.2095-3941.2024.0218
A1 Wu, Heliang
A1 Wang, Yi
A1 Lin, Yulin
A1 Ma, Ru
A1 Du, Xuemei
A1 Su, Yandong
A1 Yang, Rui
A1 Yang, Zhiran
A1 Liang, Xinli
A1 Zhang, Yinguang
A1 Liang, Xiaoqing
A1 Ji, Zhonghe
A1 Lai, Chunning
A1 Huang, Yajing
A1 Li, Yan
YR 2024
UL http://www.cancerbiomed.org/content/early/2024/11/01/j.issn.2095-3941.2024.0218.abstract
AB Objective: Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the in vitro and in vivo efficacy of natural killer (NK) cells for treatment of MPM.Methods: An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright–Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies.Results: NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice.Conclusions: NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile.The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.